This application is in response to the Paul B. Beeson Career Development Award in Aging (K23). The candidate, Dr. Angela L. Jefferson, is a clinical neuropsychologist and Assistant Professor of Neurology at Boston University School of Medicine. The research aims of this proposal are two-fold: (1) to elucidate the relations between MRI-based cardiac structure and function (left ventricular mass, ejection fraction, and cardiac output) and neuropsychological and structural brain MRI variables and (2) to relate MRI-based cardiac structure and function to longitudinal maladaptive cognitive and structural brain MRI changes. The proposed study capitalizes on existing data of the Framingham Heart Study (FHS). The FHS provides a single site, community-based sample of men and women with a wealth of antecedent and contemporary risk factor data, neuropsychological measures, and cardiac and brain MRI data. The current proposal will utilize cross-sectional and five-year longitudinal follow-up data for more than 2000 participants age 50 years and older, who are free of clinical dementia and stroke. Successful completion of this research study will establish if relations between cardiac integrity and brain changes are due to shared CVD risk factors, are relevant in those free of clinically evident CVD and dementia, are associated with accelerated brain aging over time, and are generalizable to community-based individuals. This research will yield important pathophysiological insights regarding the complex interrelations between heart structure and function and brain aging, which may contribute to improved prevention, risk stratification, and management of cardiac disease and maladaptive cognitive aging. This application proposes a parallel training plan that extends Dr. Jefferson's prior training and research activities in geriatric neuropsychology and cardiovascular disease by providing new and detailed training in (1) epidemiology, including vascular and genetic risk assessment, (2) structural neuroimaging, and (3) biology of aging, co-morbidity of age-related diseases, and clinical geriatrics. Training will involve individual and research team meetings with an interdisciplinary network of mentors, collaborators, and consultants; formal coursework in epidemiology, neuroimaging, and responsible conduct of research; educational seminars; and formal neuroimaging training activities. The integrated research and training plans outlined in this application will significantly advance Dr. Jefferson's research career and provide the skill set necessary for an independent program of patient-oriented research focused on cardiovascular risk factors for accelerating cognitive aging. [unreadable] [unreadable] [unreadable]